The invention belongs to the field of biological detection, in particular to a protein antigen composition for detecting an Alzheimer's disease autoantibody in a human serum sample and an applicationof the composition. The adopted technical scheme includes that the antigen composition comprises at least two protein fragments of the following proteins: MAPT, ADARB1, HSP60, P21, DAG, DNAJC8, RAGE,ASXL1 and JMJD2D. Based on the above antigen composition, a kit for diagnosis, especially early diagnosis of Alzheimer's disease or related risks can be prepared. By using the antigen composition, early Alzheimer's disease can be diagnosed pertinently, rapidly and accurately, and thus the composition has important practical significance.